Neuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental processes. Although
ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its expression
in aged human brain. We show that ErbB4 immunoreactivity was shown regional difference in the hippocampus
of age-matched control and that the distribution of these molecules was altered in Alzheimer’s disease (AD) brains.
Immunohistochemical characterization of the distribution of ErbB4 receptor in the hippocampus relative to pathology
staging were performed in age-matched control (Braak stage Ⅰ/Ⅱ, n=5), early AD (Braak stage Ⅲ/Ⅳ, n=5) and advanced
AD(Braak stage Ⅴ/Ⅵ, n=10). The intensity of ErbB4 immunoreactivity was higher in neurons of the CA2 than that in
CA1 or CA3 in the age-matched control. Particularly, in the early AD, ErbB4 immunoreactivity was significantly increased
in the apoptotic cells of the CA2 field. In the advanced AD, ErbB4 immunostaining was more intense in the apoptotic
cell of the CA2 field. In the dentate gyrus (DG), ErbB4-positive granular cell density was gradually increased in proportion
to the progression of pathology of AD brains. We have also found that ErbB4 immunostaining was increased in the nucleus,
suggesting that the presenilin-dependent cleavage of ErbB4 generates the soluble ErbB4 ICD (intracellular domain)
that translocalized to the nucleus. Together, these results provide the immunohistochemical analysis of ErbB4 receptor
in the human hippocampus staged by the progression of pathology of AD.